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Document 32024R1701
Commission Delegated Regulation (EU) 2024/1701 of 11 March 2024 amending Regulation (EC) No 1234/2008 as regards the examination of variations to the terms of marketing authorisations for medicinal products for human use
Commission Delegated Regulation (EU) 2024/1701 of 11 March 2024 amending Regulation (EC) No 1234/2008 as regards the examination of variations to the terms of marketing authorisations for medicinal products for human use
Commission Delegated Regulation (EU) 2024/1701 of 11 March 2024 amending Regulation (EC) No 1234/2008 as regards the examination of variations to the terms of marketing authorisations for medicinal products for human use
C/2024/1627
OJ L, 2024/1701, 17.6.2024, ELI: http://data.europa.eu/eli/reg_del/2024/1701/oj (BG, ES, CS, DA, DE, ET, EL, EN, FR, GA, HR, IT, LV, LT, HU, MT, NL, PL, PT, RO, SK, SL, FI, SV)
In force
Official Journal |
EN L series |
2024/1701 |
17.6.2024 |
COMMISSION DELEGATED REGULATION (EU) 2024/1701
of 11 March 2024
amending Regulation (EC) No 1234/2008 as regards the examination of variations to the terms of marketing authorisations for medicinal products for human use
(Text with EEA relevance)
THE EUROPEAN COMMISSION,
Having regard to the Treaty on the Functioning of the European Union,
Having regard to Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use (1), and in particular Article 23b(2a) thereof,
Having regard to Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Union procedures for the authorisation and supervision of medicinal products for human use and establishing a European Medicines Agency (2), and in particular Article 16a(3) thereof,
Whereas:
(1) |
The Union legal framework regarding variations to the terms of marketing authorisations is laid down in Commission Regulation (EC) No 1234/2008 (3). In the light of practical experience in the application of that Regulation, it is appropriate to proceed to its review in order to establish a simpler, clearer and more flexible legal framework, while guaranteeing the same level of public health protection. |
(2) |
The procedures laid down in Regulation (EC) No 1234/2008 should therefore be adjusted, without departing from the general principles on which those procedures are based. |
(3) |
In order to achieve efficiency gains and to reduce the administrative burden for the pharmaceutical industry and to better use the resources of the competent authorities, the existing legal framework should be simplified and streamlined, ensuring the same standards for quality, efficacy and safety of medicines. |
(4) |
In order to constantly take account of scientific and technical progress and to ensure the streamlined procedures of variations, the classification guidelines may need to be updated more frequently on the basis of this knowledge. For this purpose, the Agency should provide annual recommendations on unforeseen variations and any updates to be integrated in the guidelines and published in the electronic version on the Commission website. |
(5) |
Grouping of several variations in a single submission is already possible in certain cases. However, practical experience and knowledge acquired from the worksharing procedure have shown that the grouping of variations could be extended to enable more flexibility and to increase harmonisation. Therefore, the submission of a single submission of variations to the terms of more than one marketing authorisation (‘super-grouping of variations’) should be introduced in order to enable marketing authorisation holders to include their purely national marketing authorisation in the super-grouping of variations and to harmonise their purely national marketing authorisations in different Member States. |
(6) |
The variations worksharing procedure enables already today the single submission of variations to the terms of more than one marketing authorisation owned by the same marketing authorisation holder. In order to avoid duplication of work in the evaluation of variations, it should be possible for competent authorities to process all appropriate variations under the worksharing procedure. |
(7) |
Advances in science and technology and decades of experience in the manufacture of biological medicinal products enables the application of a risk-based approach for quality changes related to those biological medicinal products. Therefore, it is appropriate to adapt the approach of classifying some of the quality changes related to biological medicinal products as, by default, major variations. This will apply to all biological medicines including advanced therapy medicines. |
(8) |
Based on the experience gained from the COVID-19 pandemic and the adaptations to the variation systems that have been made to ensure the continued effectiveness of vaccines by changing their composition so as to protect against new or multiple variant strains in the context of that pandemic or otherwise, similar possibilities to change the composition should be introduced for other vaccines to address a public health emergency. |
(9) |
In line with the approach taken with human influenza vaccines, updates of human coronavirus vaccines should be streamlined outside a public health emergency. Thus, also the examination of variations concerning changes to the active substance for the purposes of the annual update of a human coronavirus vaccine should follow the same rules as influenza vaccines when the Agency considers it necessary from the public health perspective and takes into account global approaches to updates of human coronavirus vaccines. |
(10) |
It is necessary to take account of developments arising as a result of efforts to align at international level the life-cycle management of medicinal products, especially in the context of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. This may be supported by the use of additional regulatory tools, such as post-approval change management protocols. |
(11) |
Regulation (EU) 2019/5 of the European Parliament and of the Council (4) moved certain core elements of the system for examination of applications for variations provided for in Regulation (EC) No 1234/2008 into Directive 2001/83/EC and Regulation (EC) No 726/2004. A delegation of powers is conferred on the Commission in Directive 2001/83/EC and Regulation (EC) No 726/2004 to complement those core elements by laying down further necessary elements and to adapt the system for examination of applications for variations to technical and scientific progress. In order to avoid any duplication, it is appropriate to delete those elements from Regulation (EC) No 1234/2008. In view of the changes introduced by Regulation (EU) 2019/6 of the European Parliament and of the Council (5), which provides that Regulation (EC) No 1234/2008 is to no longer apply to veterinary medicinal products, any references to veterinary medicinal products should be removed from Regulation (EC) No 1234/2008. |
(12) |
A transitional period should be established in order to give all interested parties, in particular competent authorities of the Member States and the pharmaceutical industry, time to adapt to the new legal framework. |
(13) |
Regulation (EC) No 1234/2008 should therefore be amended accordingly, |
HAS ADOPTED THIS REGULATION:
Article 1
Regulation (EC) No 1234/2008 is amended as follows:
(1) |
the title is replaced by the following: ‘Commission Regulation (EC) No 1234/2008 of 24 November 2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use’; |
(2) |
Article 1 is amended as follows:
|
(3) |
Article 2 is amended as follows:
|
(4) |
in Article 3(3), point (b) is replaced by the following:
|
(5) |
Article 4 is amended as follows:
|
(6) |
Article 5 is amended as follows:
|
(7) |
the following Article 6a is inserted: ‘Article 6a Additional regulatory tools For certain changes to the chemical, pharmaceutical and biological information for a medicinal product a holder may rely on a range of process parameters, quality attributes, protocols or summary documents, upon agreement of the relevant authority and subject to the conditions referred to in the Annexes and the guidelines referred to in Article 4(1) with regard to the specific regulatory tool.’ |
(8) |
in Article 7(2), point (a) is replaced by the following:
|
(9) |
the following Article 7a is inserted: ‘Article 7a Super-grouping of variations 1. By way of derogation from Articles 7 and 13d, the holder may submit a single notification of variations to the terms of more than one marketing authorisation referred to in Chapters II, IIa and III owned by the same holder where the same or several minor variations of type IA referred to in Article 8, Article 13a or Article 14 are notified at the same time and fall within one of the cases of super-grouping of variations listed in the guidelines referred to in Article 4(1) (“super-grouping”). 2. A single notification as referred to in paragraph 1 shall be made simultaneously to the reference authority and all relevant authorities.’ |
(10) |
the title of Chapter II is replaced by the following: ‘CHAPTER II VARIATIONS TO MARKETING AUTHORISATIONS GRANTED IN ACCORDANCE WITH CHAPTER 4 OF DIRECTIVE 2001/83/EC ’; |
(11) |
in Article 8, paragraph 1 is replaced by the following: ‘1. Where a minor variation of type IA is made, the holder shall submit simultaneously to all relevant authorities a notification containing the elements listed in Annex IV. That notification shall be submitted within 12 months following the implementation of the variation as an annual update for all minor variations of type IA or be submitted as part of grouping of variations in accordance with Article 7(2), first subparagraph, points (b) and (c), or as part of super-grouping of variations in accordance with Article 7a. The notification shall be submitted immediately after the implementation of the variation in the case of minor variations requiring immediate notification for the continuous supervision of the medicinal product concerned. By way of derogation from the first subparagraph, in justified cases, the competent authority of the reference Member State may accept the immediate submission of the notification after the implementation of the variation.’ |
(12) |
in Article 10(2) is amended as follows:
|
(13) |
in Article 13, paragraphs 1 and 2 are replaced by the following: ‘1. Where recognition of a decision in accordance with Article 10(4) or approval of an opinion in accordance with Article 20(8), point (b), is not possible on grounds of a potential serious risk to public health, a relevant authority shall request that the matter of disagreement be forthwith referred to the coordination group. The party in disagreement shall give a detailed statement of the reasons for its position to all Member States concerned and to the holder. 2. Article 29(3), (4) and (5) of Directive 2001/83/EC shall apply to the matter of disagreement referred to in paragraph 1.’ |
(14) |
in Article 13a, paragraph 1 is replaced by the following: ‘1. Where a minor variation of type IA is made, the holder shall submit to the competent authority a notification containing the elements listed in Annex IV. This notification shall be submitted within 12 months following the implementation of the variation as an annual update for all minor variations of type IA or be submitted as part of grouping in accordance with Article 13d(2), first subparagraph, points (b) and (c), or as part of super-grouping of variations in accordance with Article 7a. The notification shall be submitted immediately after the implementation of the variation in the case of minor variations requiring immediate notification for the continuous supervision of the medicinal product concerned. By way of derogation from the first subparagraph, in justified cases, the competent authority of the Member State may accept the immediate submission of the notification after the implementation of the variation.’ |
(15) |
in Article 13c, paragraph 2 is amended as follows:
|
(16) |
in Article 14, paragraph 1 is replaced by the following: ‘1. Where a minor variation of type IA is made, the holder shall submit to the Agency a notification containing the elements listed in Annex IV. This notification shall be submitted within 12 months following implementation of the variation as an annual update for all minor variations of type IA or be submitted as part of grouping in accordance with Article 7(2), first subparagraph, points (b) and (c), or as part of super-grouping of variations in accordance with Article 7a. The notification shall be submitted immediately after the implementation of the variation in the case of minor variations requiring immediate notification for the continuous supervision of the medicinal product concerned. By way of derogation from the first subparagraph, in justified cases, the Agency may accept the immediate submission of the notification of the variation.’ |
(17) |
Article 16 is amended as follows:
|
(18) |
Article 17 is amended as follows:
|
(19) |
Article 18 is amended as follows:
|
(20) |
Article 20 is amended as follows:
|
(21) |
Article 21 is replaced by the following: ‘Article 21 Public health emergency 1. By way of derogation from Chapters I, II, IIa and III, where a public health emergency at Union level is recognised by the Commission pursuant to Regulation (EU) 2022/2371 of the European Parliament and of the Council (*1) the relevant authorities, or in the case of centralised marketing authorisations, the Commission may, where certain pharmaceutical, non-clinical or clinical data are missing, exceptionally and temporarily accept a variation to the terms of a marketing authorisation for a human vaccine pertaining to the pathogen causing the public health emergency. 2. The relevant authority may request the holder to provide supplementary information in order to complete its assessment within a time limit set by it. 3. Variations may be accepted pursuant to paragraph 1 only if the benefit-risk balance of the medicinal product is favourable. 4. Where a variation is accepted pursuant to paragraph 1, the holder shall submit the missing pharmaceutical, non-clinical and clinical data within a time limit set by the relevant authority. 5. In the case of centralised marketing authorisations, the missing data and the time limit for submission or compliance shall be specified in the conditions to the marketing authorisation. Where the marketing authorisation has been granted in accordance with Article 14-a of Regulation (EC) No 726/2004 this may be done as part of the specific obligations referred to in paragraph 4 of that Article. (*1) Regulation (EU) 2022/2371 of the European Parliament and of the Council of 23 November 2022 on serious cross-border threats to health and repealing Decision No 1082/2013/EU (OJ L 314, 6.12.2022, p. 26, ELI: http://data.europa.eu/eli/reg/2022/2371/oj).’;" |
(22) |
Article 22 is amended as follows:
|
(23) |
in Article 23(1a), point (a) is amended as follows:
|
(24) |
in Article 23a, the following title is inserted: ‘ Compliance with the paediatric investigation plan ’; |
(25) |
in Article 24(5), the second subparagraph is replaced by the following: ‘By way of derogation from the first subparagraph, urgent safety restrictions and variations related to safety issues which concern marketing authorisations granted in accordance with Chapter 4 of Directive 2001/83/EC shall be implemented within a time frame agreed by the holder and the competent authority of the reference Member State, in consultation with the other relevant authorities.’; |
(26) |
Article 26 is deleted; |
(27) |
Annexes I, II, and III are amended in accordance with Annex I to this Regulation; |
(28) |
Annex V is replaced by the text set out in Annex II to this Regulation. |
Article 2
This Regulation shall enter into force on the twentieth day following that of its publication in the Official Journal of the European Union.
It shall apply from 1 January 2025.
This Regulation shall be binding in its entirety and directly applicable in all Member States.
Done at Brussels, 11 March 2024.
For the Commission
The President
Ursula VON DER LEYEN
(1) OJ L 311, 28.11.2001, p. 67, ELI: http://data.europa.eu/eli/dir/2001/83/oj.
(2) OJ L 136, 30.4.2004, p. 1, ELI: http://data.europa.eu/eli/reg/2004/726/oj.
(3) Commission Regulation (EC) No 1234/2008 of 24 November 2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use and veterinary medicinal products (OJ L 334, 12.12.2008, p. 7, ELI: http://data.europa.eu/eli/reg/2008/1234/oj).
(4) Regulation (EU) 2019/5 of the European Parliament and of the Council of 11 December 2018 amending Regulation (EC) No 726/2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency, Regulation (EC) No 1901/2006 on medicinal products for paediatric use and Directive 2001/83/EC on the Community code relating to medicinal products for human use (OJ L 4, 7.1.2019, p. 24, ELI: http://data.europa.eu/eli/reg/2019/5/oj).
(5) Regulation (EU) 2019/6 of the European Parliament and of the Council of 11 December 2018 on veterinary medicinal products and repealing Directive 2001/82/EC (OJ L 4, 7.1.2019, p. 43, ELI: http://data.europa.eu/eli/reg/2019/6/oj).
ANNEX I
Annexes I, II, and III to Regulation (EC) No 1234/2008 are amended as follows:
(1) |
Annex I is amended as follows:
|
(2) |
Annex II is amended as follows:
|
(3) |
Annex III is amended as follows:
|
(*1) For parenteral administration, it is necessary to distinguish between intra-arterial, intravenous, intramuscular, subcutaneous and other routes.’;’
ANNEX II
‘ANNEX V
Variations concerning a change to or addition of therapeutic indications.
ELI: http://data.europa.eu/eli/reg_del/2024/1701/oj
ISSN 1977-0677 (electronic edition)